A drift-type ion mobility (IM) spectrometer may be coupled with a time-of-flight mass spectrometer (TOF MS) to provide unique two-dimensional information about an analyte in question. In the combined IM-TOF system, ions are separated by mobility prior to being transmitted into the TOF MS where they are mass-resolved based on their flight times to the detector. Performing the two separation techniques in tandem is particularly useful in the analysis of biopolymers such as polynucleotides, proteins, carbohydrates and the like, as the added dimension provided by the IM separation may help to mass-resolve large ions that are different from each other but present overlapping mass peaks.
While both IM and TOF MS are fast separation techniques and have typical timing parameters that make them generally compatible with each other, both techniques are inherently associated with a low duty cycle when conventionally implemented with a “pulse and wait” (or “inject and wait”) approach. In the pulse and wait approach, after an ion packet is injected into the drift tube of an IM spectrometer, the next ion packet is not injected until elution the first ion packet from the drift tube is complete, which may take several hundreds of milliseconds. In a TOF MS, under the pulse and wait approach a TOF injection pulse is not applied until the slowest ion from the previous injection pulse has reached the detector. The pulse and wait approach is conventionally done to avoid spectral overlap and thereby simplify the construction of the mass spectrum from the sample under investigation, but as already noted results in a low duty cycle.
In the combined IM-TOF system the ions eluting from the IM drift tube are transmitted into the pulser of the TOF MS, which injects the ions into the flight tube of the TOF MS. Ion flight times through the flight tube to the detector are on the order of microseconds, and often two or three orders of magnitude faster than drift times through the IM drift tube. The pulser needs to operate at a higher frequency than that of the pulse and wait approach to provide an acceptable level of detection sensitivity and avoid losing an excessive amount of ions (i.e., ions transmitted through the pulser without being injected into the flight tube of the TOF MS). The overall duty cycle of the combined IM-TOF system may be improved by “multiplexing” or “oversampling” the IM instrument (i.e., injecting ion packets into the IM drift tube at a faster rate than the total elution time of each ion packet) as well as “multiplexing” or “overpulsing” the TOF MS (i.e., injecting ion packets into the flight tube of the TOF MS at a faster rate than the total flight time of each ion packet). Multiplexing can increase sensitivity and throughput and reduce the loss of ions, but conventionally requires complex deconvolution techniques (e.g., Fourier transform techniques, Hadamard transform techniques, pseudo-random sequencing, etc.) of both the IM and TOF spectra to recover the full data and generate a meaningful mass spectrum. Double (IM and TOF) spectrum deconvolution may require costly electronics and significant real-time computational resources.
Therefore, there is a need for providing a solution for implementing ion mobility time-of-flight mass spectrometry that maximizes sensitivity without involving the complications of double spectrum deconvolution.